Damage to lungs when oxygen is inhaled at higher than normal concentrations can result in death. Yet oxygen therapy is an important treatment for several respiratory problems. The free radical theory of oxygen toxicity supposes that production of superoxide and hydrogen peroxide which occurs normally with several enzymic and non-enzymic reactions, increases in hyperoxia and overwhelms the capacity of the protective enzymes, superoxide dismutase, catalase and peroxidases. In the proposed research, we will test the free radical theory by measuring superoxide and hydrogen peroxide production and release from type II pneumocytes and macrophages in culture, in isolated perfused lungs, and in plasma, as a function of oxygen concentration. We will also compare the effects of substances which may inhibit or enhance the reactions which produce superoxide and hydrogen peroxide. The second goal of the proposed research is to determine whether protective enzymes can be induced or stabilized. Enzyme activities will be measured in cells isolated from lungs of animals exposed to graded elevations of oxygen concentration and in cells exposed to oxygen and substrates of superoxide generating systems in short term culture. The effects of inhibitors of protein synthesis and of substrates of protective enzymes on stability to proteolytic degradation will be compared.